This research project is designed to clarify the principles of making biologically functional macromolecules which are capable of both recognition and activation or particular sites within a substrate. Biological systems consist of numerous polymeric macromolecules. The role of these macromolecules is basically distinguish their corresponding target molecules and specifically interact with them in order to transfer appropriate signals derived from genes. Essentially, living organism are comprised of a network of such systems. There are several polyribonucleotides (RNA) that are capable of highly sophisticated recognition and activation of particular phosphoester bonds in substrate RNAs. The RNAs are made of only four monomer units and their sixes are relatively small. Thus they serve as ideal model systems in which to investigate biologically active macromolecules. We have been working on such an RNA, the group I intron from Tetrahymena, in order to clarify the minimum requirements for is catalytic function. We have developed simple reaction systems that we will use to complete our studies of the relationship between structure and function of the RNA catalyst. Then the catalytic function of the RNA will be systematically examined using random mutagenesis techniques. The accomplishment of this project will provide us with significant results that should allow us to understand the development of biological systems in a more generalized manner. Since all biological systems are composed of recognition and activation processes between organic molecules, this subject has broad implications, not in the fields of molecular biology and biochemistry but also in the fields of developmental biology and medicine.